Specific Reactions of Different Striatal Neuron Types in Morphology Induced by Quinolinic Acid in Rats

Qiqi Feng,Wanlong Lei,Shuhua Mu,Yuxin Ma,Si Chen,Jiajia Wu,Lisi Ouyang,Gilles J Guillemin

doi:10.1371/journal.pone.0091512

Qiqi Feng, Wanlong Lei + Show 6 more

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https://doi.org/10.1371/journal.pone.0091512

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Abstract

Huntington's disease (HD) is a neurological degenerative disease and quinolinic acid (QA) has been used to establish HD model in animals through the mechanism of excitotoxicity. Yet the specific pathological changes and the underlying mechanisms are not fully elucidated. We aimed to reveal the specific morphological changes of different striatal neurons in the HD model. Sprague-Dawley (SD) rats were subjected to unilaterally intrastriatal injections of QA to mimic the HD model. Behavioral tests, histochemical and immunhistochemical stainings as well as Western blots were applied in the present study. The results showed that QA-treated rats had obvious motor and cognitive impairments when compared with the control group. Immunohistochemical detection showed a great loss of NeuN+ neurons and Darpp32+ projection neurons in the transition zone in the QA group when compared with the control group. The numbers of parvalbumin (Parv)+ and neuropeptide Y (NPY)+ interneurons were both significantly reduced while those of calretinin (Cr)+ and choline acetyltransferase (ChAT)+ were not changed notably in the transition zone in the QA group when compared to the controls. Parv+, NPY+ and ChAT+ interneurons were not significantly increased in fiber density while Cr+ neurons displayed an obvious increase in fiber density in the transition zone in QA-treated rats. The varicosity densities of Parv+, Cr+ and NPY+ interneurons were all raised in the transition zone after QA treatment. In conclusion, the present study revealed that QA induced obvious behavioral changes as well as a general loss of striatal projection neurons and specific morphological changes in different striatal interneurons, which may help further explain the underlying mechanisms and the specific functions of various striatal neurons in the pathological process of HD.

Highlights

Huntington’s disease (HD) is an inherited neurodegenerative disorder characterized by abnormal involuntary movements and cognitive impairment [1]
The excitotoxin quinolinic acid (QA), mitochondrial toxin 3-nitropropionic acid (3NP) and transgenic models are used to study the pathophysiology of HD [9,10,11]
Behavioral impairments in QA-treated rats HD is a neurodegenerative condition characterized by progressive abnormal involuntary movements and cognitive impairment associated with perseverative behavior and impairment in strategy and planning [1,10]

Summary

Introduction

Huntington’s disease (HD) is an inherited neurodegenerative disorder characterized by abnormal involuntary movements and cognitive impairment [1]. The pathological hallmark of HD is the selective neuron death in the striatum – loss of spiny projection neurons and relative sparing of aspiny interneurons [2]. The pathogenesis of HD critically involves the mutant gene huntingtin (htt) which encodes a large protein (350 kDa) with a polyglutamine stretch [3,4]. Despite the discovery of htt, the pathophysiology of HD and the mechanisms accounting for the selective neuron death still remain unclear. It has been suggested that excitotoxicity, mitochondrial abnormalities and transcriptional dysregulation are some important mechanisms in the progress of HD [6,7,8]. The excitotoxin quinolinic acid (QA), mitochondrial toxin 3-nitropropionic acid (3NP) and transgenic models are used to study the pathophysiology of HD [9,10,11]

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